The interaction of muscle fiber contraction with the activity of the sympathetic nerves is a major determinant of vascular resistance in striated muscle. In cheek pouch arterioles, propagated vasodilation (PVD) induced with acetylcholine iontophoresis has been defined as an increase in the diameter of resistance vessels at sites well removed from the initial stimulus. A specific aim of this research proposal is to investigate PVD in response to muscle fiber contraction as a mechanism for coordinating the local control of blood flow among segments comprising the resistence network. It is hypothesized that: a) there is a threshold of striated muscle fiber activity required to induce PVD into arterioles that supply the active fibers, b) the magnitude of propagation will be related to be intensity of muscular contraction, and c) propagation functions to coordinate red cell flow (02 delivery) with local metabolic requirements of contracting fibers. Initial experiments will be performed on the hamster cremaster muscle. Muscle fibers are stimulated via microelectrodes positioned in the tissue; voltage and frequency are manipulated to control the activity of muscle fibers. Vasomotor responses, striated muscle fiber contraction, and arteriolar red cell flow are observed directly using intravital microscopy. Another aim of these studies is to investigate the interaction of PVD with sympathetic vasoconstriction (SVC). A longstanding question has focused on the "escape" of resistance vessels in active tissue from SVC, traditionally explained by local metabolic production of vasodilators. It is hypothesized that a) PVD from active tissue may interact with SVC of arterioles, and thus be an integral component of "functional sympatholysis" of microvessels, and b) feed arteries are the primary site of flow control during SVC. The interaction of PVD with SVC will be investigated in arterioles and the small feed arteries to determine if either control system dominates as a function of vessel size or location. SVC will be manipulated via the baroreflex using graded occlusions of either the carotid arteries or the inferior vena cava. These studies will illuminate the interaction of vasomotor stimuli arising from multiple locations (parenchymal cells, other vessel segments, sympathetic nerves), and define specific locations of blood flow control during muscular activity and SVC. Findings may offer novel methods for treatment of hypertension and ischemic disorders.